The purpose of this study was to evaluate the utility of combining polymer matrices to overcome extended lag periods or unacceptably short durations of action intrinsic in the individual polymer systems. Leuprolide, an LHRH superagonist, was incorporated into a variety of poly(lactide-co-glycolide) (PLGA) matrices using a solvent extraction/evaporation method. The in vitro release of Leuprolide from these matrices was evaluated at pH 7.0 and 37 degrees C in phosphate buffer. The formulations were administered to an animal model at 3 or 9 mg kg(-1) doses and serum testosterone levels were followed using a RIA method. A two-part system was made by combining microspheres made from a 75:25 acid terminated PLGA and microspheres made from a 75:25 ester terminated PLGA. This combination elicited chemical castration from 10-100 days. A three-part combination composed of an ester terminated 75:25 PLGA formulation, an ester terminated 50:50 PLGA formulation and an acid terminated 50:50 PLGA formulation also provided a composite profile with an onset of 10 days and a duration of approximately 100 days. Additionally, a single polymer system composed of a high molecular weight ester terminated 75:25 PLGA was employed to produce release over the desired 90-day release period. This study demonstrates that microsphere combinations can potentially provide effective therapies over extended intervals when combined at the proper ratio.
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http://dx.doi.org/10.1163/156856200743977 | DOI Listing |
Asian J Org Chem
January 2025
Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854, USA.
A one-pot process was developed to synthesize in moderate to high yield a series of 2-substituted indoles and 7-azaindoles starting from 2-iodo--mesylarylamines and terminal alkynes in the presence of CuO in DMF at 90-120 °C. Without isolation of any intermediate, our optimized conditions enabled the introduction of ester, phenyl, hydroxymethyl, hydroxyethyl, -Boc-aminomethyl, and methyl at the 2-postion of indoles and 7-azaindoles. The reaction tolerates a variety of substrates containing halogens, or acid- or base-sensitive functional groups without requiring a Pd catalyst, a ligand, or a base.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric OptoElectronic Materials, College of Chemistry and Molecular Sciences, and TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430072, China.
A modular platform technology for the synthesis of α-aryl carbonyl derivatives via Borono-Catellani-type secondary alkylation of arenes is presented. This practical method features a broad substrate scope regarding aryl boronic acid catechol esters, secondary alkyl bromides, and diversified terminating reagents (e.g.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Jain University - Ramanagara Campus, Centre for Nano and Material Sciences, Jakkasandra Post Kanakapura Taluk, Ramanagara-562112, Bangalore, 562112, Bangalore, INDIA.
The development of a metallic copper-based catalyst system remains a significant challenge. Herein, we report the synthesis of highly stable, active, and reusable Cu0 catalyst for the carboboration of alkynes using carbon electrophiles and bis(pinacolato)diboron (B2pin2) as chemical feedstocks to afford di- and trisubstituted vinylboronate esters in a regio- and stereoselective manner with appreciable turnover number (TON) of up to 2535 under mild reaction conditions. This three-component coupling reaction works well with a variety of substituted electrophiles and alkynes with broad functional group tolerance.
View Article and Find Full Text PDFJ Am Heart Assoc
January 2025
Division of Cardiovascular Science, Faculty of Biology, Medicine and Health The University of Manchester Manchester UK.
Background: Heart failure with preserved ejection fraction (HFpEF) is linked to prolonged endoplasmic reticulum (ER) stress. P21-activated kinase 2 (Pak2) facilitates a protective ER stress response. This study explores the mechanism and role of Pak2 in HFpEF pathology.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Key Laboratory of Applied Chemistry of Chongqing Municipality and Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
Achieving catalytic asymmetric functionalization of methylenecyclopropanes (MCPs) by selective C-C bond cleavage is a notable challenge due to the intricate reaction partners involved. In this work, we report that chiral aldehyde/palladium combined catalysis enables the asymmetric functionalization of MCPs with NH-unprotected amino acid esters. This reaction proceeds through a regiospecific branched ring-opening mechanism, resulting in optically active α,α-disubstituted α-amino acid esters bearing nonconjugated terminal alkene units.
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